This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6xhx
From Proteopedia
(Difference between revisions)
m (Protected "6xhx" [edit=sysop:move=sysop]) |
|||
| (4 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the A2058-unmethylated Thermus thermophilus 70S ribosome in complex with erythromycin and protein Y (YfiA) at 2.55A resolution== | |
| + | <StructureSection load='6xhx' size='340' side='right'caption='[[6xhx]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6xhx]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XHX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XHX FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0TD:(3S)-3-(METHYLSULFANYL)-L-ASPARTIC+ACID'>0TD</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=2MU:2,5-DIMETHYLURIDINE-5-MONOPHOSPHATE'>2MU</scene>, <scene name='pdbligand=4OC:4N,O2-METHYLCYTIDINE-5-MONOPHOSPHATE'>4OC</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=ERY:ERYTHROMYCIN+A'>ERY</scene>, <scene name='pdbligand=M2G:N2-DIMETHYLGUANOSINE-5-MONOPHOSPHATE'>M2G</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6xhx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xhx OCA], [https://pdbe.org/6xhx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xhx RCSB], [https://www.ebi.ac.uk/pdbsum/6xhx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xhx ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RL9_THET8 RL9_THET8] Binds to the 23S rRNA. Extends more that 50 Angstroms beyond the surface of the 70S ribosome.[HAMAP-Rule:MF_00503] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 A resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance. | ||
| - | + | Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance.,Svetlov MS, Syroegin EA, Aleksandrova EV, Atkinson GC, Gregory ST, Mankin AS, Polikanov YS Nat Chem Biol. 2021 Apr;17(4):412-420. doi: 10.1038/s41589-020-00715-0. Epub 2021 , Jan 18. PMID:33462493<ref>PMID:33462493</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6xhx" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Ribosomal protein THX 3D structures|Ribosomal protein THX 3D structures]] |
| - | [[Category: Mankin | + | *[[Ribosome 3D structures|Ribosome 3D structures]] |
| - | [[Category: Svetlov | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Thermus thermophilus HB8]] | ||
| + | [[Category: Aleksandrova EV]] | ||
| + | [[Category: Atkinson GC]] | ||
| + | [[Category: Gregory ST]] | ||
| + | [[Category: Mankin AS]] | ||
| + | [[Category: Polikanov YS]] | ||
| + | [[Category: Svetlov MS]] | ||
| + | [[Category: Syroegin EA]] | ||
Current revision
Crystal structure of the A2058-unmethylated Thermus thermophilus 70S ribosome in complex with erythromycin and protein Y (YfiA) at 2.55A resolution
| |||||||||||
